Abstract: The function of a biological neuronal network is determined by the intrinsic properties of its[unreadable] constituent neurons, their spatial connectivity, and the adaptive strengthening/weakening of those connections[unreadable] as informed by the network!s spatiotemporal pattern of electrical and chemical signaling. Deciphering the[unreadable] neuronal code - the rules by which spatiotemporal connectivity translates to function - remains to be a major[unreadable] scientific challenge, largely due to the lack of experimental tools that enable both the preparation of well-[unreadable] defined neuronal circuits with controlled connections and the simultaneous mapping of physical connectivity[unreadable] among, and signal propagation between, many neurons. The project proposed herein aims to develop new[unreadable] nano- and microelectronic tools that address these particular issues. Specifically, we will develop: (1) planar[unreadable] patch-clamp arrays (element number > 100, element pitch < 200 ?m) that enable the real-time monitoring of[unreadable] multiple neurons in dissociated culture or slice preparations and (2) vertical nanowire arrays that can perturb[unreadable] and modify neuronal differentiation and synapse formation through the controlled introduction of biochemical[unreadable] signals in a cell-specific fashion. These new tools will then be used, in combination with optical excitation and[unreadable] imaging schemes, to probe, at both the local and global levels, the real-time dynamics of constituent neurons[unreadable] within a given neuronal network upon application of precisely defined perturbations. Combined together, these[unreadable] tools will also provide a new platform for assaying, in a parallel fashion, the biochemical and genetic pathways[unreadable] that govern neuronal differentiation and growth. The proposed research, which combines recent advances in[unreadable] neurobiology with cutting-edge developments in nanomaterials synthesis and microfabrication, will allow for the[unreadable] meticulous study of extant network connectivity and stimuli- and reward-induced synaptic adaptation. The[unreadable] information gained through these studies will be crucial for systematically translating any network!s connectivity[unreadable] to its function, and thus help to unravel the design principles of the brain.